Status epilepticus (SE) in man and rodents can produce cognitive deficits and trigger a series of molecular and cellular events that eventually culminate in the appearance of spontaneous seizures, i.e., epilepsy. An early event in this process is the transient opening of the blood-brain barrier with consequent exchange of cells and proteins between blood and brain interstitium. Our hypothesis, supported by preliminary evidence, is that neuronal cyclooxygenase 2 (COX2) induction by status epilepticus controls the breakdown of the blood-brain barrier. Specific aims are (1) to determine whether the induction of COX2 in principal forebrain neurons in both rodent models of SE triggers a neuroinflammatory cascade that causes opening of the blood-brain barrier, peripheral leukocyte infiltration, microglial activation, and eventually epilepsy; and (2) To test the hypothesis that EP2 receptor activation on astrocytes or endothelial cells regulates albumin leakage and leukocyte infiltration across the blood-brain barrier. A comparison of the pilocarpine and kainate SE models will be done to minimize model-specific conclusions. Aim 1 will be pursued by comparing the intensity of inflammatory events following SE in wildtype mice and mice with conditional deletion of the COX2 gene limited to principal forebrain neurons. The expectation is that the broad neuroinflammatory consequences of SE will be attenuated in the COX2 cKO mouse. The second aim will be pursued by a) measuring the effect of prostaglandin receptor agonists and antagonists on the leakiness of an in vitro blood-brain barrier, and b) determining whether the neuroinflammatory consequences of SE described in aim 1 are attenuated by systemically applied EP2 antagonists.